Figure 1Endosymbiotic origins of the apicoplast of P. falciparum
The apicoplast of P. falciparum is a non-photosynthetic secondary plastid surrounded by four membranes. It is derived from two serial endosymbiotic events. The first, called primary endosymbiosis, occurred between a nucleated biciliate phagotroph and a photosynthetic cyanobacterium bounded by two membranes. This process gave rise to the three lineages of Archaeplastida: glaucocystophytes, red algae and Viridiplantae (including green algae and land plants). The second endosymbiosis involved the engulfment and retention of a red alga by a second phagotroph, which gave rise to the Chromalveolates, including P. falciparum, a parasite in the apicomplexan lineage. The outermost membrane of the secondary plastid is derived from the phagotrophic digestive vacuole that engulfed the red alga. The third membrane from the inside is called the periplastid membrane and is derived from the plasma membrane of the red alga. The first and second membranes, from the inside, are derived from the inner and outer membranes of the primary plastid respectively. As in primary plastids, the central space within the innermost membrane is called the stroma, whereas the space between the innermost and outer membrane is called the intermembrane space. The periplastid compartment, between the outer membrane and periplastid membrane, is derived from the endosymbiont cytosol and contains the nucleomorph in cryptomonads. Finally, the space between the periplastid membrane and outermost membrane is most likely to be continuous with the ER lumen. Conversion of the endosymbiont into a secondary plastid requires gene transfer from both the original plastid and the endosymbiont nucleus, now called the nucleomorph. Of the Chromalveolates, only the cryptomonads retain a nucleomorph within its secondary plastid.
Figure 2Model for protein import into the apicoplast of P. falciparum
Most apicoplast proteins traffic to the organelle with N-terminal bipartite leaders, consisting of a signal peptide and a transit peptide. The signal peptide targets the nascent apicoplast protein to the ER membrane (i), where co-translational insertion into the ER occurs via the Sec translocon (ii). The signal peptide is removed during co-translation (iii), leaving the apicoplast protein in the ER lumen with only an N-terminal transit peptide (iv). How transport from the ER lumen to the apicoplast is achieved is unclear, but may involve an apicoplast-specific ER domain (v) and vesicular transport (vi–vii). Whereas vesicle-like structures similar to (vi) have been observed for some T. gondii outermost membrane proteins, none has been documented in P. falciparum. Whether by vesicles, or another unknown mechanism, the connection between the outermost membrane and the endomembrane system means that the space between the outermost membrane and the periplastid membrane is contiguous with the ER lumen. Consequently, once apicoplast proteins, now bearing only the transit peptide, have three remaining membranes to cross. Currently, protein translocation across the periplastid membrane is postulated to occur at the recently identified symbiont-derived ERAD complex (sERAD), which is distinct from the ER-localized, host-derived ERAD (hERAD). Components of the Toc and Tic complexes are predicted to facilitate translocation across the outer and innermost membrane respectively. However, functional evidence for these translocation processes has not yet been provided in P. falciparum. Once in the stroma, the transit peptide is removed by SPP (signal peptide peptidase), allowing the mature protein to be folded by stromal chaperones (viii).